Qj9106000

From the Haemostasis, Thrombosis & Vascular Biology Unit, University Department ofMedicine, City Hospital, Birmingham, UK
The term ‘microalbuminuria’ has been introduced
thelial damage or dysfunction, such as von
to describe a measurable increase in urine albumin
Willebrand factor, suggests the possibility that
excretion, which is still within normal total urine
microalbuminuria may be a simple, cheap and easy
protein excretion levels. Many data suggest that
index of endothelial abnormalities in cardiovascular
microalbuminuria is of value as an index of vascular
disease. Nevertheless, further information on the
damage, especially in hypertension and diabetes,
value of microalbuminuria in other atherosclerotic
and there is increasing information on its associ-
vascular complications, such as ischaemic heart
ations with traditional cardiovascular risk factors
disease, stroke and peripheral artery disease is still
and its prognostic value. The association between
microalbuminuria and peripheral markers of endo-
The various components of urinary protein excretion
protein excretion in the urine. The usual screening
are useful indicators of renal function. The biggest
method for the detection of proteinuria is the
fraction of protein excreted in normal urine consists
dipstick (for example, ‘Albustix’) which has a
of Tamm-Horsfall protein, which originates from
sensitivity of 150–300 mg/l. However, even with afive-fold increase of albumin excretion, the total
renal tubular cells. Low-molecular-mass plasma
urine protein (as detected by Albustix) may remain
within normal range, and so increased levels of
albuminuria may be undetected.3 Nevertheless, such
through the glomerular basement membrane and
changes may have pathological significance. For
reabsorbed by tubular cells,1 and thus an increase
example, Viberti et al.4 showed in 1982 that
in their urinary excretion indicates tubular damage.
increased albumin levels, even within the ‘normal’
On the other hand, medium-size (40–150 kDa)
proteinuric range, may herald the onset of nephro-
plasma proteins are precluded almost completely
pathy in insulin-dependent diabetes mellitus (IDDM)
from glomerular ultrafiltrate and therefore any
patients, whilst Parving et al.5 reported in 1974 that
detection in urine of these proteins indicates
increased urine albumin excretion (UAE) can be
alteration of the glomerular barrier. Proteins such
found in poorly-controlled hypertensives. The term
albumin, transferrin, immunoglobulin G, caerulo-
‘microalbuminuria’ was therefore introduced to
plasmin, a1-acid glycoprotein and the HDL particles
describe such an increase in urine albumin
are typical examples of the latter category.2
excretion, which was still within normal total urine
Albumin is the major constituent of abnormal
Address correspondence to Dr C. Lydakis, University Department of Medicine, City Hospital, Birmingham B18 7QH.e-mail: [email protected]
cardiovascular risk in Black subjects, even with mild
increases of blood pressure, when compared with
The term ‘microalbuminuria’ was introduced by
Viberti et al.4 to refer to a subclinical rise in UAE
Age correlates positively with UAE in both normo-
>30 mg/24 h in patients with IDDM. The definition
and hypertensives, perhaps due to a degree of
has also been applied to patients with essential
nephrosclerosis that accompanies age (which is
hypertension; although the same as that used in
greater in hypertensives).21 By contrast, a negative
diabetes, this definition may not be necessarily
correlation was noted between UAE and age in the
correct. It would be more relevant to study UAE in
population study from New Zealand, which was
a large background population with exactly the same
attributed to the progressive reduction of glomerular
techniques and procedures as in essential hypertens-
ive patients, and to define abnormal albuminuria as
increased UAE rate has been reported in the erect
the level above (say) the 95th percentile.6 For
position22 and during exercise23 in both normo- and
example, in a study from the general population
with 5670 subjects (using random urine samples) inNew Zealand, the 97.5th percentile concentrationof UAE was 28 mg/l for men and 29 mg/l for women.7
The UAE rate can vary highly from day to day,
by up to 40%.8 Early-morning urine specimens have
been reported to have smaller variations,9 but large
Several methods are used for measuring UAE, such
variations in morning and night specimens have
as nephelometry,12 immunoturbidimetry,24 immuno-
previously been noted.10,11 Measurement of the 24-h
assay with latex bodies,25 radial immunodiffusion,26
urine collection has probably the lowest variability.
fluroimmunoassay,27 and enzyme immunoassay.28
In one study, for example, the coefficients of variation
Urine albumin is stable at room temperature, so
in daily, overnight and 24 h urine collections were
urine specimens can even be sent by post.29 Urine
50%, 58% and 44%, respectively.12 Due to this wide
specimens can be stored in the fridge at −4 °C for
variation, more than one urine collection has been
8 weeks, although for periods longer than 2 weeks
advocated as necessary before convincingly labelling
the addition of preservative (sodium azide) is
a patient as ‘microalbuminuric’.
Other factors should also be taken in account
An important issue in measuring urine albumin is
when evaluating patients for microalbuminuria
the high variability in the measurements within and
(MAL). For example, normal variations in UAE can
between laboratories. In a study which was designed
occur with exercise,13 with increased diuresis14 and
to estimate existing variability, aliquots with albumin
within 24 h, being higher during day than night.15
concentrations at or near the normal range were sent
The latter diurnal variation could be the result of
to five laboratories; the assays used were immunotur-
greater activity during the day or higher blood
bidimetry, enzyme immunoassay, fluoroimmuno-
pressure values throughout day time, or could simply
assay, and zone immunoelectrophoresis.30 Variability
be due to a true circadian rhythm in excretion rates.
was equally attributable to differences in precision
Furthermore, gender and obesity are also factors
of individual immunoassays and to variation within
which play a role. In a large population study from
each laboratory; however, total variance between
New Zealand, body mass index (BMI) was found to
laboratories ranged between 43.8% to 51.4%, while
correlate positively with UAE, but only for subjects
that due to within-laboratory variance ranged
of European ethnicity, and only for BMI values
between 48.6% to 56.2%, with the immunoturbidi-
>25.9 kg/m2 for men and >28.9 kg/m2 for women,
metric method having the greater variability.
with no differences between sexes.16 By contrast, astudy of 1046 non-diabetic subjects found slightlyhigher UAE values in men compared with women,and also an inverse correlation between UAE and
height.17 On the other hand, no significant correlation
between BMI and UAE was found in an Americanstudy of 1298 non-diabetics.18 Ethnicity may be
The glomerular transmembrane transport of albumin
another important factor in UAE rates. For example,
depends upon several factors: the electric charge
subjects of Asian origin (Maori and Pacific natives)
and size of the molecule, membrane status and
have been found to have greater UAE values than
specific renal haemodynamics.31 The fractional clear-
those of European origin.16 In addition, the correla-
ance of albumin, which is defined as the fraction of
tion of UAE and blood pressure is greater in Black
albumin clearance to filtration rate, is normally very
than in White subjects,19,20 consistent with the greater
low (<0.1%) due to the negative charge and to the
comparatively large molecular size of albumin (with
intrarenal vascular dysfunction exists in hyper-
a molecular mass of 69 kDa). However, albumin
excretion is altered in many physiological and patho-
Hyperfiltration may also be present in 10–15% of
newly hypertensive patients.43 In some studies ‘renalfunctional reserve’, that is, the ability of the kidneyto increase RPF and GFR through renal vasodilatationafter a protein meal, has been used to assess the
hyperfiltration status. It has been reported that renal
In hypertension, specific haemodynamic conditions
functional reserve was reduced in hypertensives with
may lead to increased albumin transmembrane
normal renal function44 and in offsprings of hyper-
escape. For example, the basic findings in hypertens-
tensive subjects.45 These observations suggest that
ives are low renal plasma flow (RPF) and increased
hyperfiltration was already present even before a
renal vascular resistance, with maintenance of the
protein meal intake, resulting in the kidney being
glomerular filtration rate (GFR), suggesting an
unable to increase the GFR further after the protein
increase in the filtration fraction (FF).32,33 This can
meal. On the other hand, other studies do not seem
be attributed either to the unimpeded transmission
of systemic blood pressure within the glomerulus, or
Indeed, blood pressure levels correlate signific-
to increased post-glomerular vasoconstriction (of the
antly with UAE in hypertensives and probably in
efferent arteriole).32 However, Hollenberg et al.34
normotensives. Both office systolic47–49 and dia-
showed that the reduction in RPF is at least a partly
stolic,49,50 as well as 24-h systolic and diastolic48,50,51
functional phenomenon, since dopamine, phentol-
blood pressure levels, have been shown to correlate
amine and acetylcholine can reverse it.
with UAE in hypertensives. Although some studies
In addition, pharmacological inhibition of the
have shown a correlation with UAE, this relationship
action of angiotensin II causes renal vasodilatation
is only with 24-h blood pressure measurements and
in hypertensives.35 Small doses of angiotensin II
not with single office values,52,53 with a regression
normally causes renal vasoconstriction in hypertens-
coefficient for this association ranging from 0.32 to
ives, but this does not appear to be the case in
0.62. The strongest correlations are seen when 24-h
normotensives.36 This might mean however that
blood pressure measurements were used, suggesting
sensitivity to angiotensin II infusion is higher in
that the 24-h ambulatory blood pressure monitoring
hypertensives than normotensives. Increased sensit-
is more reliable than casual measurements in evalu-
ivity to angiotensin II has also been documented in
ating early target-organ damage.54 Hypertensive
normotensive subjects with positive family history
subjects without the normal night time fall in blood
of hypertension, since a reduction of RPF and GFR
pressure (‘non dippers’) have higher UAE values
after infusion of this peptide was greater than in the
when compared to hypertensives with dipping
control group.37 Angiotensin II is considered to
maintain GFR (although RPF is reduced) through
Several studies in general (unselected) popula-
selective constriction of the efferent arterioles,38 thus
tions55,56 or in non-diabetic populations57,58,60 have
increasing the intraglomerular hydraulic pressure
shown either positive correlations between UAE and
and leading to increased membrane permeability to
systolic57–59 or diastolic blood pressures,55,58,59 or a
protein. In two studies, infusion of angiotensin
lack of any correlation.56,60 However, these studies
II increased proteinuria in rats,39,40 and either
collection methods, including morning or casual or
increase of membrane permeability, perhaps due to
overnight or 24-h urine collections. In the largest
an increase of membrane pore size, are the
population study from New Zealand involving 5349
subjects, using morning specimen collections, a
These pathophysiological mechanisms are closely
positive correlation was noted only with diastolic
correlated with clinical observations. Higher GFR
values have been documented in a microalbuminuricgroup of hypertensive patients when compared witha normoalbuminuric group.41 Another study in
hypertensive subjects showed that microalbuminuricsubjects had higher plasma renin activity levels after
MAL has been established as a major risk factor for
being given captopril, when compared to normo-
the evolution of overt nephropathy and other micro-
albuminurics.42 Renal vasodilatation was also less
and macroangiopathic complications in patients with
prominent in hypertensive microalbuminurics after
both insulin-dependent62 and non-insulin-dependent
captopril, compared with hypertensive normoalbumi-
diabetes.63,64 High intraglomerular pressure, hyper-
nurics.15 The latter findings indicate that a state of
filtration and increased GFR have been documented
in the early stages of nephropathy secondary
MAL in pregnant women during the third trimester
may be an early predictor of pre-eclamptic complica-
It is also well recognized that a significant associ-
tions.74 Finally, other conditions, such as exacerba-
ation exists between UAE and peripheral insulin
tions of psoriasis have been reported to correlate
resistance. In the diabetic Munich Wistar rat model,
with UAE independently of sex, age and blood
administration of insulin normalized glomerular
capillary pressure, suggesting that glomerular hyper-tension (and subsequent increased UAE) in diabetesmay be related to insulin deficiency rather than
glomerular hypertrophy.66 Insulin resistance has alsobeen associated with increased renal sodium reab-
sorption.67 These observations suggest that hyper-
insulinemia may be one causal factor for thedevelopment of MAL.
The association between MAL and cardiovascular
In a study of 333 treated hypertensives, UAE was
risk has been closely studied in hypertensives.
found to correlate with BMI, waist-to-hip ratio, fasting
However, the prevalence of MAL in hypertension
insulin levels and sum of insulin levels at times
varies in different studies from 11%47 to 40%76 or
0, 30, 60, 90 and 120 min during an oral glucose
greater, depending upon the number of patients
tolerance test (OGTT).68 In another study of 25
studied, severity of hypertension, age, race and
hypertensives and 20 controls undergoing an OGTT,
microalbuminuric hypertensives had higher values
Correlations between UAE and several cardiovas-
of insulin area-under-the-curve values, when com-
cular risk factors have been observed in hypertensive
pared to 15 normoalbuminuric hypertensives.47
patients. For example, hypertensives with MAL have
The above studies suggest that there is an
higher left ventricular mass than normoalbuminur-
association between MAL and hyperinsulinaemia,
ics.50,52 In a further study with 74 patients with
and presumably insulin resistance in hypertensive
untreated hypertension, there was a positive correla-
tion between left ventricular mass and UAE, but only
between MAL and hyperinsulinemia per se is, how-
in men and not in women.77 Hypertensives with
ever, obscure. It is possible that both these phen-
other risk factors such as smoking or hyperlipidemia
omena are genetically determined and co-segregate
show greater target organ damage in patients
in the same patient, or that hyperinsulinaemia may
with MAL, with cardiovascular disease being 50%
cause hypertension and MAL, perhaps by altering
higher in microalbuminurics.68 The levels of UAE
membrane permeability and causing renal damage;
were also significantly correlated with body mass
alternatively, they may both be a consequence of
index and waist to hip ratio, which have recognised
the same (as yet unknown) pathogenetic factor.69
The thickness of the intima and media layers of
the carotid artery is higher in microalbuminuric
hypertensives in comparison to normoalbuminuric
Several other diseases or pathological situations are
hypertensives and normotensive controls.78 In the
associated with MAL. In cases of patients suffering
same study, other cardiovascular risk factors, such
from burns, trauma,70 muscle ischaemia or pancreat-
as total cholesterol, triglycerides, lipoprotein (a),
itis high values of UAE have been reported during
insulin area-under-the-curve and glucose area-under-
the acute phase, which remain high especially if
the-curve, were significantly more prevalent among
septic or respiratory complications occur.71 MAL has
been reported during exacerbations of inflammatory
In a large study of 11 343 non-diabetic hypertens-
bowel disease72 and rheumatoid arthritis,73 and
ives from a general population sample, the preval-
remissions of these conditions are often followed by
ence of MAL was 30%.79 The analysis showed that
normalization of UAE. These observations suggest
microalbuminurics (compared to normoalbuminur-
that UAE may perhaps behave like an acute-phase
ics) had a higher prevalence of hyperlipidemia
reactant. The postulated mechanism of albumin leak-
(57.4% vs. 52.2%), coronary artery disease (31%
age through the kidney in such diseases is that there
vs. 22.4%), peripheral vascular disease (7.3% vs.
is increased microvascular permeability secondary
4.9%), myocardial infarction (7% vs. 4%) and stroke
to increased circulating inflammatory mediators, such
(5.8% vs. 4.2%). In addition, MAL was a risk factor
as the cytokines.72 MAL may thus reflect either the
which was independent of age, duration of hyper-
direct effect of cytokines on the renal matrix or
tension and degree of blood pressure elevation.
indirect effects mediated through an inflammatory
MAL has also been regarded as a marker of
cell infiltrate into the affected kidney.72
generalized endothelial damage. The latter is the
basis of the Steno hypothesis, where that the
hypertensive complications, not all the questions
transmembrane passage of albumin (which is nega-
tively charged) is facilitated when the production ofheparan sulphate (the main negatively chargedmolecule in the glomerular basement membrane) is
reduced; poor glycaemic control inhibits the
Some studies, particularly in hypertensives, imply
enzyme N-deacetylase (which is responsible for
that MAL is accompanied by higher levels of blood
heparan sulphate production).80 Transcapillary albu-
lipids.88,89 For example, UAE has been significantly
min leakage is not confined only to the glomerulus
correlated with serum triglyceride levels (even on a
but may occur also in the retina and other vascular
multivariate analysis),88 and VLDL, triglycerides and
beds.80 In support of this, increased transcapillary
lipoprotein (a).89 A large study of 11 343 non-diabetic
escape of albumin has been observed in hypertens-
hypertensives also reported that the microalbumin-
ives, contributing to the development of MAL,81,82
uric subgroup had a higher prevalence of hyperlipid-
and hypertensives with MAL have increased levels
aemia in comparison to normoalbuminurics (57.4
of von Willebrand factor, an established marker of
vs. 52.2%).70 Another report of 12 patients with
endothelial dysfunction, when compared to hyper-
tensives with normal UAE and with normotensive
of UAE, HDL, LDL and lipoprotein (a) when com-
controls.83 Furthermore, in a Japanese study where
pared with patients with salt-resistant hypertension.90
several markers of endothelial dysfunction were
By contrast, another study of 313 hypertensives
investigated in a group of 61 elderly hypertensives,
found no relationship between various lipid compon-
the microalbuminuric subgroup showed significant
elevations of activated Factor VII (FVIIa), vonWillebrand factor and thrombomodulin, comparedwith a normoalbuminuric group and a group of
patients with ‘white coat’ hypertension.84 The
Obesity is considered to be a well-recognized risk
increased levels of such markers might account for
factor for increased morbidity and mortality, usually
the higher cardiovascular risk in hypertensive
from cardiovascular complications.90–92 It has been
patients with MAL. A further assumption of the
postulated that high intake of food, including protein,
hypothesis that MAL is an index of endothelial
can lead to renal hyperfiltration and renal impair-
dysfunction is that a widespread transcapillary
ment.93 Consistent with this hypothesis, proteinuria94
escape of albumin and other plasma proteins not
and focal glomerulosclerosis have been reported in
only occurs at the capillary level but also in other
obese patients,95 with strong correlations between
parts of the vascular tree (such as the coronary
vessels) thus triggering or contributing to the
volume.96 A correlation of UAE with waist-to-hip
ratio and insulin levels has also been noted in
However, not all the evidence is fully supportive
hypertensive men68 and in obese healthy subjects.97
of generalized vascular or target-organ damage in
These findings imply that MAL may be one of the
microalbuminuric patients. For example, where
metabolic abnormalities that accompany central-type
direct vasodilatation of the forearm vascular tree
obesity; these have been included together as part
after infusion of acetylcholine and nitroprusside was
of the insulin resistance syndrome (‘syndrome X’).
measured in hypertensives and normotensives, therewere no significant differences in the type and degreeof vascular response between micro- and normoalbu-
minuric hypertensives.85 Furthermore, in a prospect-ive follow-up of 345 non-diabetic hypertensive men
In hypertensive subjects, an increased prevalence of
with several risk factors, it was observed that the
hypertensive retinopathy has been reported in mic-
increased risk for cardiovascular events occurred
roalbuminuric patients.50,98 In another study of 84
only in patients with UAE above 100 mg/12 h, corres-
poorly-controlled hypertensives, the prevalences of
ponding to macroalbuminuria rather than MAL.86
retinopathy in patients with irreversible MAL (n=
Results from the HARVEST study in 870 young
12), patients with reversible MAL (n=27) and
hypertensives (up to 45 years old) reported that no
patients with normoalbuminuria (n=45) were 85%,
significant correlation existed between left ventricular
33% and 31%, respectively.89 The significantly
mass and UAE,87 suggesting that in the initial phase
higher prevalence of retinopathy in patients with
of hypertension, renal and cardiac involvement do
irreversible (after short intensive therapy) MAL was
considered to be compatible with the hypothesis
Overall, although it is generally accepted that the
that MAL is a marker of widespread diabetic
presence of raised UAE levels increases the risk for
demonstrated in smokers irrespective of their blood
Smoking correlates positively with UAE in patientswith IDDM on univariate analysis,99,100 but not onmultivariate analysis.101 This suggests that smoking
probably plays a minor role in the evolution ofdiabetic nephropathy.
MAL can be altered by therapeutic interventions,
In the general population, however, a positive
particularly in hypertensive subjects. Indeed, the
correlation between smoking and UAE was found in
positive correlation between blood pressure levels
the New Zealand study.55 By contrast, other studies
and MAL implies that lowering of blood pressure
in hypertensive populations did not find any signific-
could reduce UAE levels as well.43 This has been
ant relationship between UAE and smoking.68,89,102
substantiated by several studies, using different anti-
Smoking status also did not appear to contribute
hypertensive drugs. An unanswered issue, however,
to UAE variation in three groups of hypertensives
is whether different classes of antihypertensive drugs
(one microalbuminuric, one normoalbuminuric and
exert different and specific actions in the kidney.
one healthy controls), once von Willebrand factor
Bianchi et al.106 studied hypertensives with four
different classes of drugs (chlorthalidone, atenolol,
nitrendipine and enalapril) given in random order
between MAL and endothelial damage or dysfunction
but despite a similar effect on blood pressure
in diabetics.103,105 Increased von Willebrand factor
lowering, only enalapril significantly reduced UAE.
levels, an index of endothelial damage, have been
Similar decreases in UAE following treatment withquinapril or captopril have been noted.107 By con-
trast, some reports suggest that the calcium antagon-ists, such as isdradipine had no significant influence
on UAE.108 These studies suggest that angiotensin-
converting-enzyme (ACE) inhibitors had a morespecific capacity to reduce UAE compared to other
antihypertensive drugs. This favourable effect may
be a consequence of the decrease in intraglomerular
pressure, and glomerular permeability or selectivity.43
By contrast, in another study mild hypertensives
were treated with 12-week courses of doxazosin,
felodipine, metoprolol and ramipril, and all four
drugs reduced both blood pressure and UAE to the
same extent. The reduction of blood pressure per se
had beneficial effects on UAE levels, irrespective of
specific drug actions.109 The authors therefore suggest
that in patients with mild hypertension but without
elevation of the filtration fraction (as is usually the
Microalbuminuria in various cardiovascular disorders
complications.Established significanceof reversibility
case with younger hypertensives), no special and
insulin levels during OGTT when compared to
expensive antihypertensive treatment (such as ACE
normoalbuminurics.60 A recent Finnish study in 1069
inhibitors) is required, in contrast to diabetic patients
non-diabetic subjects also found that high UAE
values correlated with coronary morbidity and mor-
Overall, it seems that antihypertensive therapy can
tality (with OR of 5.93 and 3.39, respectively) and
reduce high levels of UAE (to a larger or lesser
the coexistence of MAL and hyperinsulinaemia was
extent with different antihypertensive drugs). Long-
an even stronger cardiovascular risk factor.114 Finally,
term treatment would be expected to cause perman-
an British study of 1046 White non-diabetics reported
ent reduction of albuminuria and to have a beneficial
a positive correlation between UAE with blood
effect on renal haemodynamics. Hartford et al.110
pressure (in men) age, impaired glucose tolerance
showed that even 7 years of effective treatment of
and a negative correlation with height.18
hypertensive patients eventually resulted in normal-
ization of initial increased UAE levels and a decrease
normotensive non-diabetic microalbuminuric sub-
in renal vascular resistance, with no change in GFR
jects have a more atherogenic profile and tend to
compared with control subjects. Large prospective
be more insulin-resistant than normoalbuminurics.
randomized trials are needed to investigate whether
Measurement of UAE in the general population can
reduction of MAL reduces the long-term cardiovas-
thus be helpful in the evaluation of patients with
Changes in MAL in various cardiovascular disordersare likely to be more than an epiphenomenon. Data
Yudkin et al.111 in 1988 were the first to report that,
suggest that it is of value as an index of vascular
in non-diabetic subjects, UAE significantly correlated
damage, especially in hypertension and diabetes,
with prevalence of atherosclerotic arterial disease
and increasing information on its associations with
with odds ratio (OR) of 6.38, especially the risk of
traditional cardiovascular risk factors and its pro-
peripheral vascular disease (with OR of 7.72).
gnostic value is becoming available. The association
Damsgaard et al.112 also reported a decreased sur-
between MAL and peripheral markers of endothelial
vival rate in 216 microalbuminuric nondiabetics
damage or dysfunction suggests the possibility
when compared to normoalbuminuric subjects. In
that MAL may be a simple, cheap and easy measure
the large population study from New Zealand, the
of endothelial abnormalities in cardiovascular dis-
parameters that correlated positively with UAE in a
ease. This opens the possibility of assessing various
multivariate regression model) were BMI, diastolic
treatment modalities, for example, antihypertensive
pressure, smoking, sex and ethnicity, with Asians
drugs, and their effects in reversing MAL. Never-
having greater risk than subjects of European
theless, further information of the value of MAL in
origin.55,113 The strongest risk factor found for
the investigation of other atherosclerotic vascular
developing MAL was in fact the existence of hyper-
complications, such as ischaemic heart disease,
glycaemia and impaired glucose tolerance.
stroke and peripheral artery disease is still necessary.
The different prevalence of MAL among different
ethnic groups has been attributed to genetic anddietary factors as well as smoking and drinkinghabits, but may in part be associated with the
different cardiovascular risk in different ethnic
1. Kaysen JA, Myers BD, Cowser DG, Rabkin R, Felts JM.
groups. In the San Antonio Heart Study, for example,
Mechanisms and consequences of proteinuria. Lab Invest
which studied 316 non-diabetics of Spanish origin
with regard to several cardiovascular risk factors
2. Noth R, Krolewski A, Kaysen G, Meyer T, Schambelan M.
and UAE, subjects with MAL had lower HDL levels
Diabetic Nephropathy: Hemodynamic basis andimplications for disease management. Ann Intern Med
and higher blood pressure levels, triglycerides, and
the sum of insulin measurements at times 0, 30, 60
3. Shihabi Z, Konen J, O’Connor M. Albuminuria vs. urinary
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4. Viberti GC, Hill RD, Jarret RJ, Argyropoulos A, Mahmud U,
Similar results were drawn from the Mexico City
Keen H. Microalbuminuria as a predictor of clinical
Diabetes Study, where amongst 1298 non-diabetic
nephropathy in insulin-dependent diabetes mellitus.
subjects, those with MAL had lower HDL cholesterol
and higher triglycerides, fasting glucose and 2-h
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